Induction and comparison of SIV immunity in Ad5 naive and Ad5 immune non-human primates using an Ad5 [El-, E2b-] based vaccine
Induction and comparison of SIV immunity in Ad5 naive and Ad5 immune non-human primates using an Ad5 [El-, E2b-] based vaccine
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DOI：
10.1016/j.vaccine.2011.08.038
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发表时间：
2011-10-19
期刊：
影响因子：
5.5
通讯作者：
Jones, Frank R.
中科院分区：
文献类型：
--
作者：
Gabitzsch, Elizabeth S.;Xu, Younong;Jones, Frank R.
重组腺病毒血清型5（Ad 5）载体诱导针对靶抗原的免疫应答的有效性受到预先存在的或Ad 5疫苗诱导的抗载体免疫的存在的限制。Ad 5 [E1-，E2 b-]平台是一种具有额外缺失的重组Ad 5，我们先前已报道在Ad 5免疫力存在下诱导免疫应答。在Ad 5免疫非人灵长类动物（NHP）模型中，表达HIV-1 Gag的Ad 5 [E1-，E2 b-]构建体在预先存在的Ad 5免疫力存在下诱导免疫应答。在本研究中，我们通过比较Ad 5 [E1，E2 b-]-SIV-gag/nef在Ad 5 naive和Ad 5免疫NHP中诱导的细胞介导的免疫（CMI）应答来扩展这些先前的观察结果。另外，用Ad 5 [El-. E2 b-]-HIV-pol构建体，以确定在存在疫苗诱导的Ad 5免疫性的情况下是否可以诱导针对第三抗原的免疫应答。通过分泌干扰素-γ（IFN-γ）的淋巴细胞评估，针对所有三种抗原诱导阳性CMI应答。这些CMI应答在多次免疫的过程中增加，并且在Ad 5幼稚和Ad 5免疫NHP中观察到的应答谱是相似的。未观察到主要组织相容性复合体对CMI反应的影响。这些数据表明，新的基于Ad 5 [El-，E2 b-]平台的疫苗可用于同源疫苗接种方案，以在Ad 5载体免疫的存在下诱导稳健的CMI应答。(C)2011爱思唯尔有限公司保留所有权利。
The effectiveness of recombinant Adenovirus serotype 5 (Ad5) vectors to induce immune responses against targeted antigens has been limited by the presence of pre-existing or Ad5 vaccine induced anti-vector immunity. The Ad5 [E1-, E2b-] platform, a recombinant Ad5 with additional deletions, has been previously reported by us to induce immune responses in the presence of Ad5 immunity. In an Ad5 immune non-human primate (NHP) model, an Ad5 [E1-, E2b-] construct expressing HIV-1 Gag induced immune responses in the presence of pre-existing Ad5 immunity. In the present study we expand on these prior observations by comparing the cell mediated immune (CMI) responses induced by Ad5 [E1, E2b-]-SIV-gag/nef in Ad5 naive and Ad5 immune NHP. Additionally, NHP were immunized with an Ad5 [E1-. E2b-]-HIV-pol construct following two homologous administrations of Ad5 [E1-, E2b-]-SIV-gag/nef to determine if an immune response could be induced against a third antigen in the presence of vaccine induced Ad5 immunity. Positive CMI responses, as assessed by interferon-gamma (IFN-gamma) secreting lymphocytes, were induced against all three antigens. These CMI responses increased over a course of multiple immunizations and the response profiles observed in Ad5 naive and Ad5 immune NHP were similar. No influence of the major histocompatibility complex on CMI responses was observed. These data indicate that the new Ad5 [E1-, E2b-] platform based vaccine could be used for homologous vaccination regimes to induce robust CMI responses in the presence of Ad5 vector immunity. (C) 2011 Elsevier Ltd. All rights reserved.